Priming effects of repetitive transcranial magnetic stimulation on upper limb motor recovery in people with stroke

Abstract

Poststroke motor recovery relies on neuroplasticity and motor relearning. Intermittent theta burst stimulation (iTBS), a patterned repetitive transcranial magnetic stimulation (rTMS) protocol, is being commonly used to augment the efficacy of standardized motor rehabilitation for patients with stroke. New evidence shows that a priming stimulation protocol - preceding an excitatory iTBS protocol with an inhibitory continuous theta burst stimulation (cTBS) protocol (applying cTBS prior to iTBS), may stabilize and even boost the facilitatory effect of iTBS on the stimulated primary motor cortex (M1), by utilizing metaplasticity. The priming iTBS protocol may therefore show superiority on facilitating upper limb motor outcomes in patients with stroke. Sensorimotor oscillation, induced by action observation (AO) or movement execution, is a marker of cortical activation and excitability. Sensorimotor oscillation in the form of event-related desynchronization (ERD) is considered as a potential neurophysiological biomarker that can be used as an index to evaluate iTBS-induced sensorimotor neuroplasticity. Study I: Systematic Review A systematic review about the effects of movement observation on activating the mirror neuron system (MNS) in patients after stroke was conducted by the PhD student (Chapter 2 in the thesis). The review suggested that mirror visual feedback (MVF) might revise the interhemispheric imbalance after stroke by activating the MNS, thus facilitating stroke patients' motor recovery. AO might promote motor relearning in patients with stroke by activating the MNS and motor cortex. Study II: Pilot Study I The student conducted a pilot study on healthy adults to investigate the synergistic effects of iTBS with mirror training (MT) on motor performance, sensorimotor ERD, and functional connectivity and in healthy adults (Chapters 3 and 4 in this thesis). This study demonstrated that iTBS primed the participant's brain to be more receptive to MVF, as demonstrated by an increase in MVF-induced sensorimotor ERD. Besides, in contrast to sham iTBS combined with MT, iTBS combined with MT strengthened the neural networking between the bilateral premotor cortices and ipsilaterally within the motor cortex of the stimulated hemisphere. Study III: Pilot Study II The student conducted another pilot study on healthy adults to compare the effects of a priming iTBS protocol (cTBS + iTBS) with a nonpriming iTBS protocol (sham cTBS + iTBS) on modulating the sensorimotor ERD induced by movement execution and MVF-based movement observation (Chapter 5 in this thesis). This study showed that priming iTBS to the M1 had similar effects with nonpriming iTBS on enhancing sensorimotor ERD induced by MVF-based observation, while movement-related sensorimotor ERD was more enhanced by priming iTBS, specifically in the high mu band. Study IV: Main Study In the main study (Chapter 6 in the thesis), the student investigated the effects of a 10- session priming iTBS, compared to nonpriming iTBS and sham stimulation, combined with a customary robot-assisted training (RAT), on improving upper limb motor functions and modulating sensorimotor ERD in patients with stroke, using a randomized controlled trial. The findings showed that priming and nonpriming iTBS are both superior to sham stimulation in enhancing treatment gains from RAT, and patients with a higher-functioning upper limb may experience more benefits from priming iTBS. Priming iTBS may facilitate poststroke motor relearning by enhancing the permissiveness of the ipsilesional sensorimotor area to therapeutic sensory modalities, such as the MVF. The aforementioned studies presented in the thesis will contribute to the literature in the following two ways: 1) design and refinement of a novel brain stimulation protocol on theta burst stimulation, as a priming stimulation protocol; and 2) increasing the understanding of neuroplasticity and motor relearning in patients with stroke, using neurophysiological biomarkers.